RBMS2 Chemosensitizes Breast Cancer Cells to Doxorubicin by Regulating BMF Expression.
RBMS2 Chemosensitizes Breast Cancer Cells to Doxorubicin by Regulating BMF Expression.
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RBMS2 通过调节 BMF 表达使乳腺癌细胞对多柔比星化学敏感
DOI：
10.7150/ijbs.66480
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发表时间：
2022
影响因子：
9.2
通讯作者：
Ding Q
中科院分区：
文献类型：
--
作者：
Xu F;Xia T;Xu QT;Zhang X;Huang YZ;Sun X;Shi L;Zhou XJ;Wei JF;Ding Q
化疗耐药与乳腺癌患者的治疗效果和预后密切相关。越来越多的证据表明，RNA结合蛋白（RBP）在调节肿瘤细胞增殖、转移和化疗敏感性方面具有重要作用。RNA结合基序单链相互作用蛋白2（RBMS 2），一种RBP，已被认为是几种癌症中的肿瘤抑制因子。然而，其在乳腺癌患者阿霉素敏感性中的作用尚未完全揭示。本研究通过阿霉素细胞毒性试验、流式细胞术和小鼠异种移植模型研究RBMS 2对阿霉素体外和体内致敏作用的影响。采用RIP法和双荧光素酶报告基因法研究RBMS 2与BMF的关系。我们的数据表明，在乳腺癌细胞中上调RBMS 2可以增强阿霉素的敏感性，并促进阿霉素存在下的细胞凋亡，而抑制RBMS 2则表现出相反的趋势。此外，RBMS 2的这种化学增敏作用可以通过抑制Bcl-2修饰因子（BMF）来逆转。RBMS 2正调节BMF表达，并增加BMF诱导的（裂解的）caspase 3、（裂解的）caspase 9和聚（ADP-核糖）聚合酶（PARP）的表达。这些结果揭示了RBMS 2在阿霉素增敏中的新机制，表明RBMS 2可能作为耐药乳腺癌的潜在治疗靶点。
Chemoresistance is closely related to the therapeutic effect and prognosis in breast cancer patients. Increasing evidences demonstrated that RNA binding proteins (RBPs) have notable roles in regulating cancer cell proliferation, metastasis and chemotherapeutic sensitivity. RNA binding motif single stranded interacting protein 2 (RBMS2), an RBP, has been considered to be a tumor suppressor in several cancers. However, its role of doxorubicin sensitivity in breast cancer patients has not yet been fully revealed. Here, we performed doxorubicin cytotoxicity assay, flow cytometry and mouse xenograft model to examine the influence of RBMS2 on doxorubicin sensitization in vitro and in vivo. RIP assay and dual-luciferase reporter assay were performed to explore the relationship between RBMS2 and BMF. Our data demonstrated that upregulation of RBMS2 in breast cancer cells could enhance sensitivity to doxorubicin and promote apoptosis in the presence of doxorubicin, while inhibition of RBMS2 showed an opposite trend. Moreover, this chemosensitizing effect of RBMS2 could be reversed by the inhibition of Bcl-2 modifying factor (BMF). RBMS2 positively regulated BMF expression and increased BMF-induced expression of (cleaved) caspase 3, (cleaved) caspase 9 and poly (ADP-Ribose) polymerase (PARP). These results uncovered a novel mechanism for RBMS2 in the sensibilization of doxorubicin, suggesting that RBMS2 may act as a potential therapeutic target for drug-resistant breast cancer.
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DOI：
10.1038/nrc2607
发表时间：
2009-05
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.7
作者：
Ma, Xuelei;Wang, Manni;Wei, Xiawei
通讯作者：
Wei, Xiawei
影响因子：
5.9
作者：
Xi PW;Zhang X;Zhu L;Dai XY;Cheng L;Hu Y;Shi L;Wei JF;Ding Q
通讯作者：
Ding Q
Gas6/Axl 轴通过 Akt/GSK-3 β/β-连环蛋白信号传导促进乳腺癌化疗耐药和转移
影响因子：
12.4
作者：
Wang C;Jin H;Wang N;Fan S;Wang Y;Zhang Y;Wei L;Tao X;Gu D;Zhao F;Fang J;Yao M;Qin W
通讯作者：
Qin W
影响因子：
5.2
作者：
Pilco-Ferreto, Nesstor;Calaf, Gloria M.
通讯作者：
Calaf, Gloria M.